Human Immunodeficiency Virus-1 Subtype-C Genetically Diversify to Acquire Higher Replication Competence in Human Host with Comorbidities.

Abstract

Unusual disease progression is observed in the HIV-1 infected patients who are either coinfected with Mycobacterium tuberculosis (Mtb) or concomitantly on intravenous drug use (IDU). The mechanism involved in the breakdown of host immune defense and the synergistic effect in both the conditions are still not well understood. In this study, we aimed to highlight the emergence of genetically diversified variants of virus in these two cohorts among HIV-1 subtype-C infected population from a Northern state of India. A cross-sectional study was performed on treatment-naïve HIV-1 subtype-C infected individuals constituting three different cohorts of HIV-1 monoinfected, HIV-1-M. tuberculosis (HIV-TB) coinfected, and HIV-1 infected individuals on substance abuse (HIV-IDU) for acquisition of genetic alterations in terms of frequency of drug resistance (DR) mutations in reverse transcriptase gene. The data reveal a significantly higher viral load, higher death rate, and higher frequency of major DR mutations in the genome of viral isolates from HIV-TB and HIV-IDU cohorts as compared with HIV monoinfected. Majority of the mutations found in the HIV-TB coinfected and HIV-IDU cohorts conferred high level of resistance to the first-line treatment regimen (Lamivudine with Tenofovir or zidovudine or Abacavir and Nevirapine or Efavirenz). Our findings support the hypothesis that the HIV-1 evolve while replicating in the host with Mtb coinfection or substance abuse, with the emergence and accumulation of genetically diversified quasi-species. Further studies are warranted to understand the association of such genetic variations with increased replication competence and faster rate of disease progression in such individuals.